Macrolide compounds represent a well-known family of antibacterial agents. For example, erythromycin A, 14-membered macrolide, was isolated in 1952 from Streptomyces erythraeus. Examples of macrolides being used as therapeutic agents include Roxithromycin, Clarithromycin and Azithromycin (azalide). Ketolides are semisynthetic 14-membered ring macrolide derivatives, characterized by the presence of a keto function at position 3 instead of L-cladinose moiety present in the macrolactone ring. Telithromycin and Cethromycin are examples of ketolides.
U.S. Pat. No. 4,331,803 discloses 6-O-methyl derivative of erythromycin i.e. Clarithromycin. U.S. Pat. No. 4,349,545 discloses Roxithromycin. U.S. Pat. No. 4,517,359 discloses Azithromycin. Another compound, Telithromycin is described in EP 680967 A1 and corresponding U.S. Pat. No. 5,635,485 and Bioorg. Med. Chem. Lett. 1999, 9(21), 3075-3080. Another ketolide Cethromycin (ABT 773) is disclosed in WO 98/09978, and J. Med. Chem. 2000, 43, 1045.
U.S. Pat. No. 6,900,183 describes 11,12-γ lactone ketolides having C-21 of the lactone substituted with cyano or amino derivatives. Several other disclosures, including, US 2004/0077557; WO 02/16380, WO 03/42228, WO 04/16634 and WO 03/072588 disclose 11,12-γ lactone ketolides. WO 07/060518 discloses some of the intermediates useful in the synthesis of ketolides and novel ketolides.